PDBsum entry 1sjh

Immune system

PDB id: 1sjh

Contents

Protein chains

179 a.a. *

190 a.a. *

13 a.a. *

230 a.a. *

Waters ×252

* Residue conservation analysis

PDB id:

1sjh

Name:

Immune system

Title:

Hla-dr1 complexed with a 13 residue HIV capsid peptide

Structure:

Hla class ii histocompatibility antigen, dr alpha chain. Chain: a. Fragment: extracellular domain of hla-dra 0101. Synonym: mhc class ii antigen dra. Engineered: yes. Hla class ii histocompatibility antigen, drb1-1 beta chain. Chain: b. Fragment: extracellular domain of hla-drb 0101. Synonym: mhc class i antigen drb1 1, Dr-1, dr1.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: hla-dra. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Gene: hla-drb1. Synthetic: yes. Synthetic construct.

Biol. unit:

Dodecamer (from PDB file)

Resolution:

2.25Å R-factor: 0.220 R-free: 0.245

Authors:

Z.Zavala-Ruiz,I.Strug,B.D.Walker,P.J.Norris,L.J.Stern

Key ref:

Z.Zavala-Ruiz et al. (2004). A hairpin turn in a class II MHC-bound peptide orients residues outside the binding groove for T cell recognition. Proc Natl Acad Sci U S A, 101, 13279-13284. PubMed id: 15331779 DOI: 10.1073/pnas.0403371101

Date:

03-Mar-04 Release date: 17-Aug-04

Protein chain

P01903  (DRA_HUMAN) -  HLA class II histocompatibility antigen, DR alpha chain from Homo sapiens

Seq: 254 a.a.

Struc: 179 a.a.

Protein chain

P01911  (2B1F_HUMAN) -  HLA class II histocompatibility antigen, DRB1 beta chain from Homo sapiens

Seq: 266 a.a.

Struc: 190 a.a.*

Protein chain

P12495  (GAG_HV1Z2) -  Gag polyprotein from Human immunodeficiency virus type 1 group M subtype D (isolate Z2/CDC-Z34)

Seq: 501 a.a.

Struc: 13 a.a.

Protein chain

P0A0L5  (ENTC3_STAAU) -  Enterotoxin type C-3 from Staphylococcus aureus

Seq: 266 a.a.

Struc: 230 a.a.*

* PDB and UniProt seqs differ at 17 residue positions (black crosses)

DOI no: 10.1073/pnas.0403371101

Proc Natl Acad Sci U S A 101:13279-13284 (2004)

PubMed id: 15331779

A hairpin turn in a class II MHC-bound peptide orients residues outside the binding groove for T cell recognition.

Z.Zavala-Ruiz, I.Strug, B.D.Walker, P.J.Norris, L.J.Stern.

ABSTRACT

T cells generally recognize peptide antigens bound to MHC proteins through contacts with residues found within or immediately flanking the seven- to nine-residue sequence accommodated in the MHC peptide-binding groove. However, some T cells require peptide residues outside this region for activation, the structural basis for which is unknown. Here, we have investigated a HIV Gag-specific T cell clone that requires an unusually long peptide antigen for activation. The crystal structure of a minimally antigenic 16-mer bound to HLA-DR1 shows that the peptide C-terminal region bends sharply into a hairpin turn as it exits the binding site, orienting peptide residues outside the MHC-binding region in position to interact with a T cell receptor. Peptide truncation and substitution studies show that both the hairpin turn and the extreme C-terminal residues are required for T cell activation. These results demonstrate a previously unrecognized mode of MHC-peptide-T cell receptor interaction.

Selected figure(s)

Figure 2.
Fig. 2. Crystal structures of DR1/Gag[PP16]/SEC3 and DR1/Gag[PG13]/SEC3. (A) A |2 F[o] - F[c]| electron density map calculated by using model phases and contoured at 1 for the Gag[PP16] complex in the vicinity of the peptide. Carbon atoms are yellow, nitrogen atoms are blue, and oxygen atoms are red. (B) Corresponding map of the Gag[PG13] complex, but with carbon atoms being green. (C) Surface of HLA-DR1 showing superposition of bound Gag[PP16] (yellow) and Gag[PG13] (green) peptides. (D and E) Difference Fourier map|F[Gag[PP16]] - F[Gag[PG13]]| calculated by using Gag[PP16] model phases, contoured at 4 , with positive (Gag[PP16]) density in yellow and negative (Gag[PG13]) density in green, overlaid with the Gag[PP16] peptide (D) or the Gag[PG13] peptide (E). No significant positive or negative difference peaks were observed outside this region.

Figure 3.
Fig. 3. A type II -turn at the C-terminal region of the Gag[PP16] peptide. (A) C-terminal region of the DR1 peptide-binding site with bound Gag[PP16] peptide showing conserved MHC peptide hydrogen bonds. Conserved MHC peptide hydrogen bonds in this region are shown as gray dashed lines, with the Gag[PP16] intraturn hydrogen bond between the nitrogen of Ala (P12) and the carbonyl oxygen of Ser (P9) shown as a red dashed line. (B) Closeup view of the Gag[PP16] hairpin, showing the intraturn hydrogen bond and - values characteristic of a type II -turn. (C) Alignment of HLA-DR crystal structures exhibiting ordered peptide density beyond P10. Complexes were aligned by least-squares fitting of 1 and 1 domains. Peptides are shown as C traces. DR1/TP1 is red (PDB ID code 1KLU [PDB] ), DR2a/MBP is blue (PDB ID code 1FV1 [PDB] ), DR3/CLIP is magenta (PDB ID code 1A6A [PDB] ), DR1/Ha is cyan (PDB ID code 1DLH [PDB] ), DR2a/EBV is gray (PDB ID code 1H15 [PDB] ), and DR4/collagen is orange (PDB ID code 2SEB [PDB] ).

Figures were selected by the author.